The novel substrates for tyrosine kinases eps8 and eps15 have been further characterized. with particular relevance to their physiological function. role in neoplasia and protein-protein interactions. A high resolution two-dimensional gel electrophoresis system has been established for analysis of phosphorylation events triggered by the erbB- 2 and epidermal growth factor receptor (EGFR) kinases. For the first time. biochemical correlates for the different biological activities of these two receptors have been identified. Analysis of the signal transduction pathway of the ret receptor-like kinase was undertaken. Also the role of ret in several human neoplastic and non-neoplastic diseases has been analyzed.